Factors affecting lipid metabolism in the heart will be investigated through the use of the vitro perfused heart system. The interaction of hormones and metabolites (ketone bodies) with neutral lipid mobilization in the perfused heart will be examined. Since genetic mouse models of obesity and/or diabetes are available, regulatory mechanisms of lipid mobilization show to be of importance in the normal heart will also be investigated in hearts of these models. Recently we have shown that heart neutral lipids are increased several-fold in the genetic obese mouse (C57BL/6J ob/ob). Since many of the metabolic abnormalities exhibited by the mouse such as insulin resistance and increased heart triglycerides are similar to human maturity-onset diabetes, investigation of the factors responsible for the increased heart triglyceride levels observed in the genetic obese mouse may yield insight as to the cause of the cardiovascular complications observed in human diabetes. BIBLIOGRAPHIC REFERENCES: Jesmok, G.J., Calvert, D.N. and Lech, J.J.: The effect of inotropic agents on glycerol release and protein kinase activity ratios in the isolated perfused heart. J. Pharm. Exp. Ther. 200: 187-194, 1977. Hron, W.T., Jesmok, G.J., Lombardo, Y.B., Menahan, L.A. and Lech, J.J.: Dependency of hormone stimulation of glycerol release on perfusate (Ca ions) in the isolated perfused rat heart. J. Mol. Cell. Cardiology, 1977, in press.